A bone defect resulting from open bone trauma may easily become infected; however, the administration of efficacious systemic antibiotics cannot be performed at safe levels. Previous studies have investigated anti-infective biomaterials that incorporate into bone and facilitate the direct application of high-concentration local antibiotics. In the present study, the effect of a novel porous composite with gentamicin sulfate (GS) in treating infected femoral condyle defects was investigated using a rat model. A novel porous composite biomaterial was prepared based on a supercritical carbon dioxide fluid technique that combined GS, demineralized bone matrix (DBM) and polylactic acid (PLA). A rat femoral condyle fracture model of infection was established. The GS/DBM/PLA composite biomaterial was implanted and its physicochemical characteristics, biocompatibility and ability to facilitate repair of infected bone defect were assessed. The GS/DBM/PLA composite biomaterial maintained the antibiotic activity of GS, with good anti-compression strength, porosity and biocompatibility. The results of the animal experiments indicated that the GS/DBM/PLA composite biomaterial exerted marked anti-infective effects and facilitated bone defect repair, while simultaneously controlling infection. Porous GS/DBM/PLA is therefore a promising composite biomaterial for use in bone tissue engineering.

The ability of non-steroidal anti-inflammatory drugs (NSAIDs) to modulate γ-aminobutyrate (GABA)-activated currents via Ca2+-activated Cl- channels in rat dorsal root ganglion neurons (DRG), was examined in the present study. During the preparation of DRG neurons harvested from Sprague-Dawley rats, the whole-cell recording technique was used to record the effect of NSAIDs on GABA-activated inward currents, and the expression levels of the TMEM16A and TMEM16B subunits were revealed. In the event that DRG neurons were pre-incubated for 20 sec with niflumic acid (NFA) and 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) prior to the administration of GABA, the GABA-induced inward currents were diminished markedly in the majority of neurons examined (96.3%). The inward currents induced by 100 µmol/l GABA were attenuated by (0±0.09%; neurons = 4), (5.32±3.51%; neurons = 6), (21.3±4.00%; neurons = 5), (33.8±5.20%; neurons = 17), (52.2±5.10%; neurons = 4) and (61.1±4.12%; neurons = 12) by 0.1, 1, 3, 10, 30 and 100 µmol/l NFA, respectively. The inward currents induced by 100 µmol/l GABA were attenuated by (13.8±6%; neurons = 6), (23.2±14.7%; neurons = 6) and (29.7±9.1%; neurons = 9) by 3, 10 and 30 µmol/l NPPB, respectively. NFA and NPPB dose-dependently inhibited GABA-activated currents with half maximal inhibitory concentration (IC50) values of 6.7 and 11 µmol/l, respectively. The inhibitory effect of 100 µmol/l NFA on the GABA-evoked inward current were also strongly inhibited by nitrendipine (NTDP; an L-type calcium channel blocker), 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis (a highly selective calcium chelating reagent), caffeine (a widely available Ca2+ consuming drug) and calcium-free extracellular fluid, in a concentration-dependent manner. Immunofluorescent staining indicated that TMEM16A and TMEM16B expression was widely distributed in DRG neurons. The results suggest that NSAIDs may be able to regulate Ca2+-activated chloride channels to reduce GABAA receptor-mediated inward currents in DRGs.

Angiogenesis is vital in tissue engineering and the size of the capillary lumen diameter directly affects vascular function. Therefore, the involvement of the pH in the regulation of the capillary lumen diameter was investigated in the present study. The cytosolic pH of different pH medium groups was measured using flow cytometry. Bromodeoxyuridine staining and wound-healing assays were performed to detect cell proliferation and migration, respectively. The expression of angiogenesis-related genes was detected using reverse transcription-quantitative PCR. In addition, cell tube formation under different pH conditions was assessed using a tube formation assay and a 3D Matrigel® model. The results indicated that a change in the pH value of the culture medium affected the cytosolic pH of the endothelial cells, which then led to a change in vascular diameter. When the medium's pH ranged from 7.4 to 7.6, the diameter of the lumen formed in the Matrigel was suitable for capillary formation in tissue engineering. The present results revealed an important role for the pH in the process of capillary formation and provided insight for pH regulation during endothelial cell tube formation and angiogenesis in tissue engineering.

Obesity and dyslipidemia are two metabolic syndrome disorders that have serious effects on the health of patients. Purinergic 2X receptor ligand-gated ion channel 7 (P2X7R) has been reported to play a role in regulating lipid storage and metabolism. However, the role and potential mechanism of P2X7R in adipogenesis and lipid degradation remain unknown. In the present study, a mouse model of obesity was established by feeding mice a high-fat diet, and the 3T3-L1 cell line was used to analyze the function of P2X7R in vitro. Reverse transcription-quantitative PCR and western blot analyses were performed to detect the expression levels of P2X7R, sterol regulatory element-binding protein 1 (SREBP1) and other associated transcription factors. Bioinformatics analysis was used to predict the potential target gene of P2X7R and a dual luciferase reporter assay was used to confirm this prediction. Oil Red O staining was used to evaluate the adipogenic capacity of preadipocytes. AdipoRed assay, cholesterol assay and a free glycerol reagent were used to measure the expression levels of triglyceride (TGs), total cholesterol (TC) and glycerin, respectively. The results indicated that P2X7R was highly expressed in obese mice and that it was involved in adipogenic differentiation in vitro. SREBP1 enhanced the transcription activities of P2X7R to promote its expression. Inhibition of P2X7R significantly reduced the adipogenic capacity of preadipocytes, decreased the expression levels of adipogenesis-associated transcription factors (peroxisome proliferator-activated receptor γ, CCAAT-enhancer-binding protein α and fatty-acid-binding protein 4), enhanced the expression levels of lipolytic enzymes (adipose triglyceride lipase, phosphorylated hormone-sensitive lipase and monoacylglycerol lipase) and regulated the expression of TG, TC and glycerin in mature 3T3-L1 cells. These effects were reversed by a small interfering RNA targeting Wnt3a. Therefore, the results suggested that P2X7R, the transcription activities of which were regulated by SREBP1, regulated adipogenesis and lipid degradation by targeting SREBP1, indicating its potential effects on obesity-associated metabolism.

The novel orally available inhibitor of the molecular chaperone heat shock protein 90 (Hsp90), BIIB021, induces the apoptosis of various types of tumor cell in vitro and in vivo. However, the effects and mechanisms of this agent on myelodysplastic syndrome (MDS) cell lines remain unknown. The aim of this study was to investigate the effects of BIIB021 on SKM-1 cells (a MDS cell line) and examine its mechanisms of action. The results showed that BIIB021 inhibited the growth of SKM-1 cells effectively in vitro. The treatment of SKM-1 cells with BIIB021 resulted in the inhibition of cell growth through G0/G1-phase cell cycle arrest and induced apoptosis by activating caspase-3, -8 and -9. Furthermore, this study also demonstrated that the mechanisms of apoptosis in SKM-1 cells were associated with the suppression of the phosphatidylinositide 3-kinase/Akt and nuclear factor-κB signaling pathways. Therefore, the findings indicate a novel approach for the treatment of high-risk MDS.

The association of functional polymorphisms in the promoter of the apoptosis gene FAS with systemic lupus erythematosus (SLE) susceptibility has been a controversial subject. We conducted a case-control study to investigate this association in a Chinese population and performed a meta-analysis in different populations. The single nucleotide polymorphisms (SNPs) rs2234767 (-1377G>A) and rs1800682 (-670A>G) were genotyped by TaqMan allelic discrimination assays in 552 Chinese SLE patients and 718 healthy controls. In our case-control study, we observed allelic association between the promoter SNP rs2234767 [P=0.033, odds ratio (OR)=0.836, 95% confidence interval (CI), 0.709-0.986] and SLE but not the SNP rs1800682. Haplotype analysis revealed that one haplotype of GA was significantly associated with the disease (P=0.039, OR=1.184, 95% CI, 1.009-1.391). In the meta-analysis available studies, including our data, were combined using the STATA software package v.7.0. The meta-analysis revealed a significant association between FAS polymorphisms and SLE (rs2234767 A vs. G allele; P=0.004, OR=0.819, 95% CI, 0.715-0.938, rs1800682 G vs. A allele: P=0.034, OR=0.791, 95% CI, 0.637-0.983). In conclusion, FAS gene polymorphisms may contribute to SLE susceptibility in the Chinese population, and the meta-analysis shows that FAS polymorphisms may be associated with SLE susceptibility in different populations.

The purpose of this study was to determine whether high-intensity focused ultrasound (HIFU) is an effective treatment for pancreatic cancer in an athymic nude mouse model. Female athymic nude mice (n=44) were inoculated subcutaneously with 5-7×10(6) SW1990 human pancreatic cancer cells. Thirty-six animals developed tumours and were randomly divided into three groups: HIFU (n=18), sham treatment (n=9) and control (n=9). The sonographic appearance of the tumours during therapy was recorded. After therapy, the tumours were examined transcutaneously by ultrasound every 4 days for 4 weeks. Tissue samples were taken from the treatment sites and histopathologically examined by light or electron microscopy. Two weeks after HIFU treatment, a 100% reduction in tumour volume was observed in all animals in the HIFU group, whereas tumours in the sham-treated and control groups continued to grow. Pathological examination of HIFU-treated tumour tissue samples showed complete coagulation necrosis in the tumour. Our results indicate that HIFU appears to be an effective therapy for pancreatic tumours in an athymic nude mouse model. Thus, the treatment may hold promise for the clinical treatment of late-stage and recurrent pancreatic cancer.

The aim of the present study was to explore the infection route of ventilator-associated pneumonia (VAP) and assess the effectiveness of a combined nursing strategy to prevent VAP in intensive care units. Bacteria from the gastric juice and drainage from the hypolarynx and lower respiratory tracts of patients with VAP were analyzed using genome macrorestriction-pulsed-field gel electrophoresis (GM-PFGE). A total of 124 patients with tracheal intubation were placed in the intervention group and were treated with a combined nursing strategy, comprising mosapride (gastric motility stimulant) administration and semi-reclining positioning. A total of 112 intubated patients were placed in the control group and received routine nursing care. The incidence rate of VAP, days of ventilation and mortality rate of patients were compared between the two groups. The GM-PFGE fingerprinting results of three strains of Pseudomonas aeruginosa from the gastric juice, subglottic secretion drainage and drainage of the lower respiratory tract in patients with VAP were similar across groups. The number of days spent on a ventilator by patients in the intervention group (7.37±5.32 days) was lower compared with that by patients in the control group (12.34±4.98 days) (P<0.05). The incidence rate of VAP was reduced from 40.81 to 21.25% following intervention with the combined nursing strategy (P<0.05); furthermore, the mortality rate of intubated patients in the intervention group was 29.46%, a significant reduction compared with the 41.94% mortality rate observed in the control group (P<0.05). Gastroesophageal reflux (GER) was confirmed as one of the infection routes for VAP. The combined nursing strategy of gastric motility stimulant administration and the adoption of a semi-reclining position was effective in preventing VAP by reducing the occurrence of GER.

Liver cancer is a highly lethal malignancy. Despite considerable efforts made in recent years, the prognosis of patients with liver cancer remains poor. Curcuma zedoaria (known as Ezhu in Chinese) is widely prescribed in traditional Chinese medicine. Germacrone (GM) is a sesquiterpene constituent derived from the essential oil of Ezhu, and exerts anti-carcinogenic effects by inducing apoptosis in various cancer cells. The present study investigated the potential mechanism of GM in HepG2 cells. Cell Counting Kit-8, colony-formation and lactate dehydrogenase-release assays, as well as cell death assays using flow cytometry, were performed to evaluate HepG2 cell proliferation following GM treatment. HepG2 cells were transfected with caspase-3 small interfering RNA and then treated with GM. Caspase-3 expression levels were determined by reverse transcription-quantitative PCR and western blotting. The present study showed that GM inhibited the growth of HepG2 cells and induced the proteolytic cleavage of caspase 3, with concomitant cleavage of gasdermin E (GSDME), by markedly increasing the production of reactive oxygen species (ROS). This led to caspase 3-dependent cleavage of GSDME, thereby promoting pyroptosis in HepG2 cells. However, these changes were rescued by ROS scavengers, such as N-acetylcysteine. Furthermore, GM inhibited tumor growth by promoting the cleavage of caspase 3 and GSDME in HepG2 cell xenograft models. These results indicated that GM induced GSDME-dependent pyroptosis through caspase 3 activation, at least in part, by damaging the mitochondria and enhancing ROS production, thereby supporting the possible development of GM as a candidate for the prevention and treatment of liver cancer.

Drug abuse is a public health and social problem. A number of studies have reported that drug addiction is associated with microRNAs (miRNAs). By comparing the expression of miRNAs in the serum exosomes of methamphetamine-dependent and ketamine-dependent rats, the aim of the present study was to provide insights into the miRNA-mediated associations between the two groups. Published results on conditioned place preference (CPP) in rats conditioned by methamphetamine and ketamine were replicated. The expression of miRNAs in serum exosomes were determined by gene-chip sequencing. The potential target genes of differentially expressed (DE) co-miRNAs were predicted in the methamphetamine and ketamine rats, then functional analysis of their target genes was performed. Methamphetamine and ketamine reward greatly increased the activity time and distance in the intrinsically non-preferred side of the behavioral apparatus when compared with controlled rats (P<0.01). In addition, methamphetamine upregulated the expression of 276 miRNAs and downregulated 25 miRNAs, while ketamine only downregulated the expression of 267 miRNAs. Ten DE co-miRNAs in the two model groups were identified. Functional analysis revealed that DE co-miRNAs are involved in the development of addiction at different stages, and their target genes were enriched in 'vesicular transport', 'amphetamine addiction', 'dopaminergic synapse' and 'GABAergic synapse'. Therefore, it was suggested that these co-miRNAs may have a strong association with drug addiction, and they may be involved in the different addiction processes, which partly explains methamphetamine and ketamine addiction.

The resistance to chemotherapeutic drugs is a critical feature of breast cancer recurrence and metastasis. Long non-coding RNAs (LncRNAs) serve key roles in tumor drug resistance. LncRNA-HOX transcript antisense RNA (HOTAIR) has been reported to be overexpressed in certain types of cancer and may be closely associated with tumor resistance. The current study aimed to investigate the role of lncRNA-HOTAIR in the regulation of breast cancer resistance to doxorubicin (DOX). A breast cancer cell line (MCF-7) and DOX-resistant breast cancer cell line (DOXR-MCF-7) were utilized in the current study. DOXR-MCF-7 cells were transfected with lncRNA-HOTAIR small interfering RNA (siRNA) and control siRNA. Subsequently, MTT and colony formation assays were performed to assess cell proliferation. Cell apoptosis was also evaluated via flow cytometry. In addition, western blotting and reverse transcription-quantitative polymerase chain reaction were performed to detect the expression of caspase-3, B-cell lymphoma 2, Bcl-2-associated X protein, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT) and mechanistic target of rapamycin (mTOR), and the phosphorylation of PI3K, AKT, and mTOR. The data indicated that lncRNA-HOTAIR silencing decreased cell proliferation and increased apoptosis in MCF-7 and DOXR MCF-7 cells. Furthermore, lncRNA-HOTAIR silencing significantly decreased the phosphorylation of PI3K, AKT and mTOR, indicating that the knockdown of lncRNA-HOTAIR effectively attenuates the resistance of breast cancer cells to DOX by inhibiting the PI3K/AKT/mTOR pathway. In summary, the present study indicated that the knockdown of lncRNA-HOTAIR weakened the resistance of breast cancer cells to DOX via PI3K/AKT/mTOR signaling, suggesting that lncRNA-HOTAIR may be a novel intervention target to reverse DOX-resistance in breast cancer.

Hydrogen sulfide (H2S), an endogenous gasotransmitter, possesses multiple physiological and pharmacological properties including anti-apoptotic, anti-oxidative stress and cardiac protective activities in diabetic cardiomyopathy. An increasing body of evidence has suggested that signal transducer and activator of transcription 3 (STAT3) has beneficial effects in the heart. However, the effect of diabetes on the phosphorylation or activation of cardiac STAT3 appears to be controversial. The present study was designed to investigate the precise function of the STAT3/hypoxia-inducible factor-1α (HIF-1α) signaling pathway in high glucose (HG)-induced H9c2 cardiomyocyte injury and the function of the STAT3/HIF-1α pathway in the cardioprotective action of H2S. The results revealed that GYY4137 pretreatment substantially ameliorated the HG-induced decrease in cell viability and the increase in lactate dehydrogenase (LDH) release in H9c2 cells. Additionally, HG treatment resulted in the upregulation of the phosphorylated (p)-STAT3/STAT3 ratio and HIF-1α protein expression in H9c2 cells, indicating that the activation of the STAT3/HIF-1α pathway was induced by HG. STAT3/HIF-1α pathway inhibition induced by transfection with STAT3 small interfering (si)-RNA attenuated the HG-induced downregulation of cell viability and the upregulation of LDH release. Furthermore, STAT3 siRNA transfection and GYY4137 pretreatment combined attenuated HG-induced apoptosis as illustrated by the decrease in the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells, caspase-3 activity, apoptosis ratio and BCL2 associated X, apoptosis regulator/BCL2 apoptosis regulator ratio in H9c2 cells. In addition, STAT3 siRNA transfection and GYY4137 blocked HG-induced oxidative stress as evidenced by the decrease in reactive oxygen species generation, malondialdehyde content and NADPH oxidase 2 expression, and the increase in superoxide dismutase activity and glutathione level. Notably, GYY4137 pretreatment was revealed to reduce the p-STAT3/STAT3 ratio and HIF-1α protein expression, resulting in the inhibition of the STAT3/HIF-1α signaling pathway in HG-treated H9c2 cells. Altogether, the present results demonstrated that H2S mitigates HG-induced H9c2 cell damage, and reduces apoptosis and oxidative stress by suppressing the STAT3/HIF-1α signaling pathway.

Diabetic nephropathy is one of most frequent complications of diabetes, and is the major cause of end-stage disease in diabetic patients. The present study investigated the roles and mechanisms of Rhein-8-O-β-D-glucopyranoside (Rg) protecting human mesangial cells (HMCs) from high glucose (HG)-induced apoptosis. Using a Cell Counting Kit-8 assay the proliferation of HMCs was analyzed, and flow cytometry was applied to detect apoptosis. The apoptosis-associated protein Bcl-2, caspase-3 and members of the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway were analyzed using a western blotting assay. HG significantly induced HMC apoptosis, and Rg markedly attenuated the HG-induced apoptosis. HG decreased the Bcl-2 expression and increased the caspase-3 expression, and Rg treatment recovered the expressions of Bcl-2 and caspase-3 affected by HG. The underlying mechanisms were further analyzed, and it was demonstrated that HG significantly upregulated the long intervening non-coding RNA (lincRNA) ANRIL expression level, downregulated let-7a expression and activated the TGF-β1/Smad signaling pathway; Rg treatment recovered the expressions of lincRNA ANRIL and let-7a, and inhibited the TGF-β1/Smad signaling pathway in the condition of HG. In conclusion, the present results suggested that Rg attenuated HG-induced apoptosis of HMCs by regulating the lincRNA ANRIL/let-7a/TGF-β1/Smad signaling pathway.

A critical event in cardiac fibrosis is the transformation of cardiac fibroblasts (CFs) into myofibroblasts. MicroRNAs (miRNAs) have been reported to be critical regulators in the development of cardiac fibrosis. However, the underlying molecular mechanisms of action of miRNA (miR)-26b in cardiac fibrosis have not yet been extensively studied. In the present study, the expression levels of miR-26b were downregulated in isoproterenol (ISO)-treated cardiac tissues and CFs. Moreover, miR-26b overexpression inhibited the cell viability of ISO-treated CFs and decreased the protein levels of collagen I and α-smooth muscle actin (α-SMA). Furthermore, bioinformatics analysis and dual luciferase reporter assays indicated that Kelch-like ECH-associated protein 1 (Keap1) was the target of miR-26b, and that its expression levels were decreased in miR-26b-treated cells. In addition, Keap1 overexpression reversed the inhibitory effects of miR-26b on ISO-induced cardiac fibrosis, as demonstrated by cell viability, and the upregulation of collagen I and α-SMA expression levels. Furthermore, inhibition of Keap1 expression led to the activation of nuclear factor erythroid 2-related factor 2 (Nrf2), which induced the transcriptional activation of antioxidant/detoxifying proteins in order to protect against cardiac fibrosis. Taken together, the data demonstrated that miR-26b attenuated ISO-induced cardiac fibrosis via the Keap-mediated activation of Nrf2.

Cisplatin (DDP) is a commonly used chemotherapy drug; however, the side effects associated with its use, particularly acute kidney injury (AKI), limit its clinical application. Puerarin is a natural flavonoid extracted from the Chinese medical herb Radix puerariae, which has been reported to alleviate DDP-induced nephrotoxicity. However, the mechanisms underlying puerarin regulation on microRNA (miR)-31-mediated signaling pathways in AKI remain unknown. Thus, the present study aimed to investigate the function of puerarin in a DDP-induced AKI rat model via reverse transcription-quantitative PCR and western blot analyses. The results demonstrated that DDP upregulated the levels of miR-31 in a concentration-dependent manner, both in vitro and in vivo. Furthermore, DDP significantly increased blood urea nitrogen and malondialdehyde content, serum creatinine and histopathological changes, while significantly decreasing the expression levels of superoxide dismutase, catalase and glutathione S-transferase in kidney tissues. TUNEL and western blot analyses indicated that DDP increased the expression levels of apoptotic proteins and affected the Numb/Notch1 signaling pathway, which is downstream of miR-31. The effects induced by DDP were counteracted following treatment with puerarin. Taken together, the results of the present study suggest that puerarin exhibits a renal protective effect against DDP-induced AKI by upregulating miR-31 expression and inhibiting the Numb/Notch1 signaling pathway.

The aim of the present study was to verify the pro-apoptotic anticancer potential of several 5,8-dimethoxy-1,4-phthoquinone (DMNQ) derivatives in Ras-mediated tumorigenesis. MTT assays were used to detect cellular viability and flow cytometry was performed to assess intracellular reactive oxygen species (ROS) levels and apoptosis. The expression levels of proteins were detected via western blotting. Among the 12 newly synthesized DMNQ derivatives, 2-benzylthio-5,8-dimethoxynaphthalene-1,4-dione (BZNQ; component #1) significantly reduced cell viability both in mouse NIH3T3 embryonic fibroblasts cells (NC) and H-RasG12V transfected mouse NIH3T3 embryonic fibroblasts cells (NR). Moreover, BZNQ resulted in increased cytotoxic sensitivity in Ras-mutant transfected cells. Furthermore, the reactive oxygen species (ROS) levels in H-RasG12V transfected HepG2 liver cancer cells (HR) were significantly higher compared with the levels in HepG2 liver cancer cells (HC) following BZNQ treatment, which further resulted in increased cellular apoptosis. Eliminating cellular ROS using an ROS scavenger N-acetyl-L-cysteine markedly reversed BZNQ-induced cellular ROS accumulation and cell apoptosis in HC and HR cells. Western blotting results revealed that BZNQ significantly downregulated H-Ras protein expression and inhibited the Ras-mediated downstream signaling pathways such as protein kinase B, extracellular signal-related kinase and glycogen synthase kinase phosphorylation and β-catenin protein expression. These results indicated that the novel DMNQ derivative BZNQ may be a therapeutic drug for Ras-mediated liver tumorigenesis. The results of the current study suggest that BZNQ exerts its effect by downregulating H-Ras protein expression and Ras-mediated signaling pathways.

Infantile haemangioma (IH) is a benign vascular tumour type that occurs in 3-10% of infants. In the present meta-analysis, previous studies comparing clinical outcomes, including the recovery rate and haemangioma activity score (HAS), adverse effects and relapse rates, were compared between patients treated with atenolol and those treated with propranolol for IH. A systematic search in various databases, including Medline, Cochrane Controlled Register of Trials, ScienceDirect and Google Scholar from inception until July 2019 was performed. The Cochrane risk of bias tool was used to assess the quality of published trials. A meta-analysis with a random-effects model and reported pooled mean differences (MD) or odds ratios (OR) with 95% CIs was performed. In total, 8 studies including 608 participants were analyzed. Only 2 studies were randomized controlled trials, while the majority of studies had low or unclear bias risks. Except for the response to medication (pooled OR=1.49; 95% CI, 0.85-2.18), all other outcomes (HAS, adverse reactions and relapse rate) were better for the atenolol group than the propranolol group. Atenolol resulted in better HAS (pooled MD=0.16; 95% CI, -0.42 to 0.73). Propranolol had more adverse reactions (pooled OR=2.17; 95% CI, 0.93-5.06) and a higher relapse rate (pooled OR, 1.67; 95% CI, 0.44-6.41) when compared to atenolol. However, these findings were not statistically significant. The results of this analysis suggest that atenolol may be non-inferior to propranolol and may offer advantages, including lower adverse reactions and relapse rates.

Non-small cell lung cancer (NSCLC) is a common malignancy associated with poor clinical outcomes and high mortality rate. The association between NSCLC development and long non-coding RNA (lncRNA) expression remains to be elucidated. The current study investigated the role of a novel lncRNA, receptor activator of nuclear factor-κ B ligand (RANKL), in the resistance of NSCLC to chemotherapy. RANKL expression was assessed via reverse transcription-quantitative PCR, cell death rate was evaluated using flow cytometry and sensitivity of cisplatin (DDP)-resistant A549/DDP cells to chemotherapy was determined using the Cell Counting Kit-8 assay. Western blotting was performed to quantify p53 protein levels. Compared with matched A549 cells, A549/DDP cells exhibited significant upregulation of RANKL expression. Sensitivity of A549/DDP cells to DDP was restored following RANKL knockdown. A549 cells overexpressing RANKL exhibited notably impaired DDP sensitivity compared with controls. Conversely, downregulated RANKL expression triggered cell death and inhibited cell migration via p53 stimulation and phosphatidylinositol 3-kinase/protein kinase B pathway suppression. The current findings indicate that RANKL contributes to DDP resistance in NSCLC and may represent a novel therapeutic target in this malignancy.

Heart failure (HF) is a global pandemic cardiovascular disease with increasing prevalence, but the pathogenesis remains to be elucidated. The present study aimed to investigate the underlying mechanism in heart failure (HF) using bioinformatics and experimental validation. A HF-associated dataset GSE84796 was downloaded from the Gene Expression Omnibus database and differentially expressed genes (DEGs) were screened for using Bayes method in the Limma package. Kyoto Encyclopedia of Genes and Genomes pathway analysis was used to perform pathway enrichment analysis of these DEGs using The Database for Annotation, Visualization and Integrated Discovery. A protein-protein interaction (PPI) network of DEG-encoded proteins was subsequently constructed using the Search tool for the Retrieval of Interacting Genes/Proteins, and a transcription factor (TF)/miRNA-target network was constructed according to the WEB-based Gene SeT AnaLysis Tookit. The expression levels of microRNA (miRNA/miR)-155, G-protein coupled receptor 18 (GRP18) and E26 transformation-specific transcription factor 2 (ETS2) were analyzed in clinical HF samples, and functional validations were performed in H9c2 (2-1) cells. A total of 419 DEGs were identified, including 366 upregulated genes and 53 downregulated genes. The upregulated DEGs were significantly enriched in the pathways of 'cytokine-cytokine receptor interaction', 'natural killer cell mediated cytotoxicity' and 'primary immunodeficiency'. A total of two functional modules were identified in the PPI network: Module A was enriched in 3 KEGG pathways and module B was enriched in 15 KEGG pathways. Furthermore, a total of three miRNAs and eight TFs were identified in the TF/miRNA-target network. Specifically, GPR18 was discovered to be targeted by both ETS2 and miR-155. Clinical validation revealed that the expression levels of miR-155 were significantly decreased in the HF samples, whereas the expression levels of ETS2 and GPR18 were significantly increased in HF samples. In conclusion, the present study suggested that GPR18 may be a target of ETS2 and miR-155, and miR-155 may regulate cell viability and apoptosis in H9c2 (2-1) cells through targeting and regulating GPR18.

The present study investigated the effect and underlying mechanisms of ginsenoside Rg1 (Rg1) in attenuating subacute liver injury induced by D-galactose (D-gal) in mice. Specific Pathogen Free (SPF) male C57BL/6J mice were randomly divided into 3 groups: i) D-gal-administration group (D-gal group), where the mice were intraperitoneally administrated with D-gal (120 mg/kg/day for 42 days); ii) D-gal + Rg1 group where the mice were treated with 120 mg/kg/day D-gal for 42 days and with Rg1 at a dose of 20 mg/kg/day for 35 days. The first dose of Rg1 was administered on the 8th day of treatment with D-gal; and iii) the normal control group, where the mice were injected with an equal volume of saline for 42 days. The day following the final injections in all groups, peripheral blood was collected and serum was prepared to measure the contents of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBiL), advanced glycation end products (AGEs) and 8-hydroxy-2 deoxyguanosine (8-OH-dG). Liver tissue homogenates were prepared to measure the contents of malondialdehyde (MDA) and glutathione (GSH), and the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). Paraffin section were prepared to observe the microscopic structure of the liver. Transmission electron microscopy was used to observe the ultrastructure of hepatocytes. Frozen section were prepared and stained with senescence-associated β-galactosidase to detect the relative optical density value of senescence-associated markers. Compared with the D-gal group, the contents of AST, ALT, TBiL, AGEs and MDA significantly decreased in the D-gal + Rg1 group, while the activities of SOD and GSH-Px markedly increased, and liver injury and degenerative alterations of hepatocytes were reduced. Administration of Rg1 induced a protective effect on D-gal-induced liver injury in mice by inhibiting the oxidative stress, reducing DNA damage and decreasing the AGE content.